A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background: As <jats:sup>225</jats:sup>Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an <jats:sup>225</jats:sup>Ac-labeled radiopharmaceutical can be accurately calculated.Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is &lt; 3%. A measurement of RCP &gt; 90% at this time point predicts a true RCP &gt; 97%.Conclusions: RCP of <jats:sup>225</jats:sup>Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.</jats:p>

PSMA-GCK01: A Generator-Based99mTc/188Re Theranostic Ligand for the Prostate-Specific Membrane Antigen

“…The ligand showed a relatively high plasma-protein binding of 98%. However, it is well-known for other PSMA ligands that high plasma-protein binding does not necessarily impose a problem for clinical application, recently even dedicated albumin-binding motifs have been suggested as an improvement when PSMA-ligands should be labeled with long physical half-life nuclides (24,25). More importantly, the free fraction in plasma did not show any signs of decomposition over a period of 4 hours.…”

Aktuelle radiopharmazeutische Entwicklungen für die theranostische Anwendung

“…1), d. h. sie emittieren im Laufe ihres radioaktiven Zerfalls zu anderen Radionukliden auch γund β --Strahlung [35]. Dies ist bei der Qualitätskontrolle des Radiopharmakons [36] und bei der Anwendung zu berücksichtigen.…”

Aktuelle radiopharmazeutische Entwicklungen für die theranostische Anwendung

“…1), d. h. sie emittieren im Laufe ihres radioaktiven Zerfalls zu anderen Radionukliden auch γ-und β --Strahlung [35]. Dies ist bei der Qualitätskontrolle des Radiopharmakons [36] und bei der Anwendung zu berücksichtigen.…”